Tyler Jacks is a cancer research pioneer, one of the co-chairs of the White House’s ambitious Cancer “Moonshot” initiative, and has helped advise a number of companies developing cancer drugs over the years. But only now is Jacks building a cancer drug maker of his own: a stealthy startup called Dragonfly Therapeutics.
Dragonfly was formed in July 2015 by Jacks, together with his longtime friend, filmmaker and tech entrepreneur Bill Haney, and UC Berkeley immunologist David Raulet. The startup has toiled along relatively quietly outside of a few announcements about its board. It’s still just a 10-employee company with labs at two incubators in Cambridge, MA—LabCentral, and Cambridge BioLabs—and is likely years away from producing data from its drugs in human patients. Yet the startup has some noteworthy power behind it.
Harold Varmus, a Nobel Prize winner and the former director of the National Cancer Institute, and K. Dane Wittrup, a protein engineering specialist and the co-founder and chief scientific officer of Adimab, are both on Dragonfly’s scientific advisory board. And according to Haney, Dragonfly’s CEO, the startup already has years of financial runway thanks not to venture capitalists, as is typical in biotech, but to a small group of family offices, one of which is associated with Tim Disney, the great-nephew of Walt Disney.
That was a purposeful decision. Haney first reached out to families he’s worked with before and got funding for Dragonfly quickly—he wouldn’t say how much, though. The speed of the funding is “not usually the case with venture firms,” he says, adding that the financing structures VC firms can insist on, like Series A, B, C rounds and so on, can lead to tension and different incentives for different investors in a syndicate. He says Dragonfly doesn’t have that kind of financial pressure, thanks to its family office backers, and could return to them for more support when needed.
“We were very focused on maintaining control and executing our plan, and we think that gives us our best chance of doing that,” Jacks says.
They were able to do this because Jacks, Raulet, and Haney already had the experience and access to networks and resources that VCs typically bring to the table. For example, Tim Disney is a college friend of Haney’s from their undergrad days at Harvard University. Raulet and Jacks met one another at MIT two decades ago and stayed in contact; their scientific work is the basis of Dragonfly. And Jacks and Haney were college roommates and have remained friends, frequently catching up to play squash, poker, and sharing Red Sox tickets. They have different specialties—Haney has become a filmmaker and startup creator, and Jacks a world-renowned scientist—but have now connected as co-founders of Dragonfly. Jacks originally kicked around the idea of Dragonfly with Raulet, and then got Haney involved during a chat at opening day at Fenway Park last year.
Haney has helped form more than a dozen tech companies, most recently Blu Homes, a developer of eco-friendly houses. But he’s less experienced in life sciences, where he’s done primarily non-profit work at the Koch Institute and elsewhere and was a founding investor in Ironwood Pharmaceuticals (NASDSAQ: IRWD). He’s never taken an operational role in biotech.
“Steve Jobs and Bill Gates didn’t have a lot of background as software entrepreneurs or consumer electronics mavens before they started,” Haney says. “A lot of the qualities of building a successful startup are universal.”
Meanwhile, Jacks has been working in cancer research for decades. In the 1990s, he helped pioneer genetically engineered mouse models of human cancer that are now used by researchers around the world. He has been the director of the David H. Koch Institute for Integrative Cancer Research at MIT since its founding in 2007, is a member of the National Academy of Sciences, and has been a consultant or board member for several life sciences companies, including Thermo Fisher Scientific and Amgen. And though he’s been a co-founder of a startup before—diagnostics company T2 Biosystems—Dragonfly is the first company based on research out of his own lab.
“I’m not just a co-founder on paper,” Jacks says. “My connection is deeper, and my investment is deeper. My engagement is more extensive. I’ve just more involved than I have been in the past.”
Unsurprisingly, given Jacks’s and Raulet’s backgrounds in cancer and immunology, the company is developing cancer immunotherapy treatments—drugs that spur on the immune system to fight cancer.
Progress in immunotherapy over the past several years has started to change the way certain cancers are treated, but there is still a long way to go. So-called checkpoint inhibitors, which help unmask tumors so the immune system can fight them, for instance, have racked up FDA approvals in skin, kidney, and other cancers, but “the ugly truth,” as Haney says, is that most patients don’t respond to them. Researchers and firms across the globe are trying to figure out why, and unearth the best way to counteract the tricks cancer uses to evade our body’s defenses.
The latest cancer immunotherapy reality check came last week, when Bristol-Myers Squibb (NYSE: BMY) disclosed that nivolumab (Opdivo), the top-selling checkpoint inhibitor, failed a Phase 3 trial in lung cancer. The news was a setback for Bristol, of course, but more broadly speaking, it offered further evidence that checkpoint inhibitors will likely need help from other drugs to boost their effectiveness. That means a huge opportunity remains for companies that can produce the best pairing for drugs like nivolumab and Merck’s (NYSE: MRK) rival pembrolizumab (Keytruda).
Opdivo’s failure, “while surprising, is not shocking, in that we’re still learning how to use these therapies,” Jacks says.
Enter the newer wave of companies and immunotherapy approaches, like the one Dragonfly is developing. Several of these companies are trying to bring the innate immune system—our body’s first line of defense against foreign invaders—into the cancer fight. Checkpoint blockers affect T cells, members of the adaptive immune system, which learns to remember threats and eliminates them when they return. But there are potentially powerful cancer killers in the innate immune system as well—macrophages, neutrophils, and more—and in the Boston area alone, companies like Jounce Therapeutics, Surface Oncology, and ImmuneXcite are trying to develop drugs that spur them on. These startups have gotten the backing of large companies like Celgene, Novartis, and Sanofi.
Dragonfly’s focus is on natural killer (NK) cells, innate immune system sentinels that help the body battle viruses, parasites, and tumors, and alert other immune cells of threats. The company’s name is a nod to NK cells; Haney calls dragonflies pound for pound “as ferocious as anything in nature.” UC Berkeley’s Raulet is an expert in NK cell research, and Jacks has been focusing on their role as cancer fighters and immune cell recruiters. Dragonfly says it is developing biologic drugs that simultaneously target NK cells and cancer. Jacks won’t divulge specifics, but he calls the drugs “biological linker molecules” that connect NK cells to tumor cells. When this happens, the NK cells both fight the tumor cells and bring T cells into the mix.
“They substantially enhance the performance of the immune system, and they’re powerful killers on their own basis,” Haney says of NK cells. “In that sense they offer things that T cells don’t.”
Such a powerful tool comes with risks—what if too strong of an immune storm is created, for instance? And other players, such as France’s Innate Pharma and Los Angeles-based NantKwest, are developing methods of activating NK cells or stimulating them with drugs. But Haney says getting NK cells to “be productive, stay productive, and not be disruptive” forms the basis of the new company. If Dragonfly can prove this concept, the strategy might apply to a broad range of cancers, he says.
“We think we’ve got a bit of an edge based on what we’ve done and how we’re thinking about it,” Jacks says.
Dragonfly is anywhere from six to 12 months away from having its first drug programs, Haney says, so it will likely be a while before the company produces human clinical data. And Jacks acknowledges that until that data arises there is a “burden of proof” to show that NK cells can provide the cancer-fighting punch Dragonfly believes they can.
“The same was true of T cells if you dial the clock back 10 or 15 years ago,” Jacks says. “There was skepticism, and then everything flipped.”